The overall aim is to develop information providing understanding of the biologic effect of thyroxine at a molecular level. Models under study during the current and past year include the following: (1) rat liver polysomal peptide elongation; thyroxine is shown to promote peptidyl t-RNA translocation from the aminoacyl to the peptidyl site on the ribosome; (2) sodium-potassium pump and lactate production by normal, human RBC; 5 X 10 to the minus 7th power M thyroxine added in vitro stimulates lactate production by such RBC. Sodium flux studies are in progress; (3) rat liver microsome fatty acid synthesis; thyroxine added in vitro appears to stimulate electron transport from DPNH flavoprotein to cytochrome b5 and independently to stimulate the terminal mixed function oxidase involved in fatty acid desaturation; (4) rat liver microsome cholesterol synthesis; thyroxine inhibits the incorporation of acetyl CoA into cholesterol but not the incorporation of mevalonate; current investigations include attempts to ascertain whether unsaturated fatty acid may inhibit acetyl CoA incorporation since it is demonstrated that thyroxine stimulates production of unsaturated fatty acids; (5) rat liver and muscle alpha glycerophosphate dehydrogenase activity; thyroxine and starvation both stimulate increase in activity of liver mitochondrial alpha glycerophosphate dehydrogenase; the effect of thyroxine is not specific and has been related to a starvation-like effect; (6) rat muscle actomyosin ATP induced superprecipitation; thyroxine promotes more protracted, perhaps more intense superprecipitation without increased ATP hydrolysis; (7) influence of thyroxine analogues on carbonyl excitation; the carbonyl excitation signal of acetone at 1726 wave numbers undergoes a red shift to 1707 wave numbers in the presence of thyroxine analogues.